NEET MDS Lessons
General Pathology
ADRENAL INSUFFICIENCY
Adrenocortical hypofunction is either primary (adrenocrtical) or secondary (ACTH deficiency). Primary insufficiency is divided into acute & chronic.
Acute Adrenocortical Insufficiency occurs most commonly in the following clinical settings
- massive adrenal hemorrhage including Waterhouse-Friderichsen syndrome
- Sudden withdrawal of long-term corticosteroid therapy
- Stress in those with chronic adrenal insufficiency
Massive adrenal hemorrhage may destroy the adrenal cortex sufficiently to cause acute adrenocortical
insufficiency. This condition may occur
1. in patients maintained on anticoagulant therapy
2. in postoperative patients who develop DIC
3. during pregnancy
4. in patients suffering from overwhelming sepsis (Waterhouse-Friderichsen syndrome)
Waterhouse-Friderichsen syndrome is a catastrophic syndrome classically associated with Neisseria meningitidis septicemia but can also be caused by other organisms, including Pseudomonas species, pneumococci & Haemophilus influenzae. The pathogenesis of the syndrome remains unclear, but probably involves endotoxin-induced vascular injury with associated DIC.
Chronic adrenocortical insufficiency (Addison disease) results from progressive destruction of the adrenal cortex. More than 90% of all cases are attributable to one of four disorders:
1. autoimmune adrenalitis (the most common cause; 70% of cases)
2. tuberculosis &fungal infections
3. AIDS
4. Metastatic cancers
In such primary diseases, there is hyperpigmentation of the skin oral mucosa due to high levels of MSH (associated with high levels of ACTH).
Autoimmune adrenalitis is due to autoimmune destruction of steroid-producing cells. It is either isolated associated other autoimmune diseases, such as Hashimoto disease, pernicious anemia, etc.
Infections, particularly tuberculous and fungal
Tuberculous adrenalitis, which once was responsible for as many as 90% of cases of Addison disease, has become less common with the advent of antituberculous therapy. When present, tuberculous adrenalitis is usually associated with active infection elsewhere, particularly the lungs and genitourinary tract. Among fungi, disseminated infections caused by Histoplasma capsulatum is the main cause.
AIDS patients are at risk for developing adrenal insufficiency from several infectious (cytomegalovirus, Mycobacterium avium-intracellulare) and noninfectious (Kaposi sarcoma) complications.
Metastatic neoplasms: the adrenals are a fairly common site for metastases in persons with disseminated carcinomas. Although adrenal function is preserved in most such patients, the metastatic growths sometimes destroy sufficient adrenal cortex to produce a degree of adrenal insufficiency. Carcinomas of the lung and breast are the major primary sources.
Secondary Adrenocortical Insufficiency
Any disorder of the hypothalamus and pituitary, such as metastatic cancer, infection, infarction, or irradiation, that reduces the output of ACTH leads to a syndrome of hypoadrenalism having many similarities to Addison disease. In such secondary disease, the hyperpigmentation of primary Addison disease is lacking because melanotropic hormone levels are low.
Secondary adrenocortical insufficiency is characterized by low serum ACTH and a prompt rise in plasma cortisol levels in response to ACTH administration.
Pathological features of adrenocortical deficiency
- The appearance of the adrenal glands varies with the cause of the insufficiency.
- In secondary hypoadrenalism the adrenals are reduced to small, uniform, thin rim of atrophic yellow cortex that surrounds a central, intact medulla. Histologically, there is atrophy of cortical cells with loss of cytoplasmic lipid, particularly in the zonae fasciculata and reticularis.
- In primary autoimmune adrenalitis there is also atrophy of the cortex associated with a variable lymphoid infiltrate that may extend into the subjacent medulla. The medulla is otherwise normal.
- In tuberculosis or fungal diseases there is granulomatous inflammatory reaction. Demonstration of the responsible organism may require the use of special stains.
- With metastatic carcinoma, the adrenals are enlarged and their normal architecture is obscured by the infiltrating neoplasm.
Lupus erythematosus
- chronic discoid lupus is primarily limited to the skin, while SLE can involve the skin and other systems.
- pathogenesis: light and other external agents plus deposition of DNA (planted antigen) and immune complexes in the basement membrane.
Histology:
- basal cells along the dermal-epidermal junction and hair shafts (reason for alopecia) are vacuolated (liquefactive degeneration)
- thickening of lamina densa as a reaction to injury.
- immunofluorescent studies reveal a band of immunofluorescence (band test) in involved skin of chronic discoid lupus or involved/uninvolved skin of SLE.
- lymphocytic infiltrate at the dermal-epidermal junction and papillary dermis.
Infections caused by gonorrhea
1. Acute urethritis. Mostly in males. Generally self-limiting. Dysuria and purulent discharge.
2. Endocervical infection. Purulent vaginal discharge, abnormal menses, pelvic pain. Often co-infection with other STD’s. Some women are asymptomatic.
3. Pelvic Inflammatory Disease (PID). Consequence of ascending endocervical infection. Causes salpingitis, endometriosis, bilateral abdominal pain, discharge, fever. May lead to sterility, chronic pain, and ectopic pregnancy because of loss of fallopian cilia.
4. Anorectal inflammation. Mostly in homosexual men. Pain, itching, discharge from anus.
5. Dermatitis/arthritis. Occurs after bacteremia. Skin will have papules on an erythematous base which develop into necrotic pustules. Asymmetric joint pain. These infections are susceptible to penicillin.
6. Neonatal infections. Ophthalmia neonatorum is a conjunctival infection from going through infected vagina. After one year of age, suspect child abuse.
NEOPLASIA
An abnormal. growth, in excess of and uncoordinated with normal tissues Which persists in the same excessive manner after cessation of the stimuli which evoked the change.
Tumours are broadly divided by their behaviors into 2 main groups, benign and malignant.
|
Features |
Benign |
Malignant |
|
General Rate of growth Mode of growth |
Slow Expansile |
Rapid Infiltrative |
|
Gross Margins
Haemoeehage |
Circumscribed often Encapsulated Rare |
III defined
Common |
|
Microscopic Arrangement Cells
Nucleus Mitosis |
Resemble Parent Tissues Regular and uniform in shape and size Resembles parent Cells Absent or scanty |
Varying degrees of structural differentiation Cellular pleomorphism
Hyper chromatic large and varying in shape and size Numerous and abnormal |
Through most tumours can be classified in the benign or malignant category . Some exhibits an intermediate behaviours.
CLASSIFICATION
|
Origin |
Benign |
Malignant |
|
Epithelial Surface epithelium Glandular epithelium Melanocytes |
Papilloma Adenoma Naevus |
Carcinoma Adenoca cinoma Melanocarcinoma(Melanoma) |
|
Mesenchymal
Adipose tissue Fibrous tissue Smooth tissue Striated muscle Cartilage Bone Blood vessels Lymphoid tissue |
Lipoma Fibroma Leiomyoma Rhabdomyoma Chondroma Osteoma Angioma
|
Liposarcoma Fibrosarcoma Leimyosarcoma Chondrosarcoma Osteosarcoma Angiosarcoma Lymphoma |
Some tumours can not be clearly categorized in the above table e.g.
- Mixed tumours like fibroadenoma of the breast which is a neoplastic proliferation of both epithelial and mesenchmal tissues.
- Teratomas which are tumours from germ cells (in the glands) and totipotent cells
(in extra gonodal sites like mediastinun, retroperitoneum and presacral region). These are composed of multiple tissues indicative of differentiation into the derivatives of the three germinal layers.
- Hamartomas which are malformations consisting of a haphazard mass of tissue normally present at that site.
Liver cirrhosis
It is a chronic, progressive diffuse process characterized by
a. Hepatocellular necrosis
b. Replacement by fibrosis and inflammation
c. Hyperplasia of surviving liver cells forming regenerating nodules
d. Vascular derangement.
All these changes lead to loss of the normal liver architecture.
Pathology of cirrhosis
At first the liver is enlarged or of normal size. Late in the disease, it is reduced in size and weight.
Consistency- Firm.
Colour -May be yellow (fatty change), red (congestion), green (cholestaisis), or pale gray (recent nodules due to absence of pigment).
Morphologically According to the size of these nodules, cirrhosis can be classified
Micronodular (regular) cirrhosis. Small nodules 2-3 mm.in diameter.
Macronodular (irregular) cirrhosis, nodules up to one cm in diameter.
Mixed cirrhosis is the end stage of all types of cirrhosis
Microscopic picture
1 Regenerating nodulesn- Proliferated hepatocytes arranged in thick plates and separated by blood sinusoids. Central vein in abnormal sites (eccentric) - Hepatocytes may be small , large , or binucleated
2- Fibrosis- It replaces damaged hepatocytes. It develops at certain sites:-
a-perivenular b -perisinusoidal c -pericellular and d -in relation to portal tracts.
- It may be young, cellular and highly vascular or mature with diminished vasculsarity. It encloses groups of hepatocytes, lobules or regenerating nodules.
-As a result of hepatocyte injury and fibrosis, there’s loss of normal liver architecture including the lobular and acinar pattern as well as the liver cell plates
3- Bile ductular proliferation:- Occurs in the fibrous septa.Focal choestaisis with feathery degeneration of hepatocytes occur at the margins of regenerating nodules. It becomes diffuse terminally.
4- Inflammatory cells:- Lymphocytes, macrophages and plasma cells infiltrate the fibrous septa and regenerating nodules
Etiological classification of cirrhosis
Congenital Occurs at childhood
- congenital syphilis
Hereditary diseases:-
a. Primary idiopathic haemochromatosis b. Thalassemia c. Wilson’s disease d.α 1-antitrypsin deficien e. glycogen storage disease
Acquired
-Cryptogenic (10-50%).
-Alcoholic (30-70%)
-Post viral (15-20%)
- Biliary cirrhosis (16%) primary or secondary.
Monocytosis:
Causes
-Infections causing lymphocytosis, especialy tuberculosis and typhoid.
-Monocytic leukaemia.
-Some auto immune diseases.
HERPES ZOSTER (Shingles)
An infection with varicella-zoster virus primarily involving the dorsal root ganglia and characterized by vesicular eruption and neuralgic pain in the dermatome of the affected root ganglia.
caused by varicella-zoster virus
Symptoms and Signs
Pain along the site of the future eruption usually precedes the rash by 2 to 3 days. Characteristic crops of vesicles on an erythematous base then appear, following the cutaneous distribution of one or more adjacent dermatomes
Eruptions occur most often in the thoracic or lumbar region and are unilateral. Lesions usually continue to form for about 3 to 5 days
Geniculate zoster (Ramsay Hunt's syndrome) results from involvement of the geniculate ganglion. Pain in the ear and facial paralysis occur on the involved side. A vesicular eruption occurs in the external auditory canal, and taste may be lost in the anterior two thirds of the tongue